Viruses often manipulate their host cellular environment in order to create favorable conditions for viral replication and survival. Virally-induced changes include alteration of the host cell cycle progression, signal transduction cascades, and transcriptional functions, among others. Epstein-Barr virus (EBV) is a human herpesvirus that infects approximately 90 percent of the world's population. EBV is the causative agent of infectious mononucleosis, and is associated with several forms of cancer, including Burkitt's lymphoma and nasopharyngeal carcinoma. EBV also produces oral hairy leukoplakia in AIDS patients. Interestingly, while infection with EBV is widespread, only certain populations of people seem to be susceptible to EBV-related cancers. To understand how EBV proteins interact with host cellular proteins, and how such interactions may promote disease, we have introduced the EBV immediate-early BZLF1 protein into the model organism Drosophila, and will perform genetic screens to identify cellular proteins that modulate Z activity. We will carry out an Fl screen of 20,000 flies, map the resulting modifiers, and determine if these modifying genes have human homologs. This work will produce a plethora of putative EBV enhancers or suppressors, which will be the basis for much future work. The results from this genetic screen will shed light onto the mechanisms by which EBV alters normal cellular functions, as well as how genetic predisposition may play a role in EBV-related diseases.